Reactome | PTCH is internalized

PTCH is internalized

Stable Identifier

R-HSA-5632677

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

ciliary membrane

ReviewStatus

5/5

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After SMURF-dependent ubiquitination, PTCH1 is internalized to endocytic vesicles for degradation (Rohatgi et al, 2007; Huang et al, 2013; Yue et al, 2014). PTCH1 and SMO show reciprocal changes in localization upon Hh pathway activation, with PTCH moving from the primary cilium to internal vesicles while SMO becomes enriched in the primary cilium after ligand binding (Denef et al, 2000; Rohatgi et al, 2007; Corbit et al, 2005; Kovacs et al, 2008; reviewed in Goetz and Anderson). In mice, internalization of PTCH1 appears to be independent of SMO, while in flies, activated SMO is required to promote the SMURF-dependent downregulation of PTCH (Yue et al, 2014; Huang et al, 2013).

Literature References

PubMed ID	Title	Journal	Year
16136078	Vertebrate Smoothened functions at the primary cilium Stainier, DY, Singla, V, Norman, AR, Reiter, JF, Aanstad, P, Corbit, KC	Nature	2005
24925320	Requirement of Smurf-mediated endocytosis of Patched1 in Sonic Hedgehog signal reception Zhang, YE, Shen, QH, Tang, LY, Chen, Y, Yue, S, Zhang, Z, Tang, Y, Tang, Y, Ding, J, Cheng, SY, Yu, TT	Elife	2014
18497258	Beta-arrestin-mediated localization of smoothened to the primary cilium Chen, W, Liu, R, Kim, J, Wang, J, Chen, M, Whalen, EJ, Kovacs, JJ, Lefkowitz, RJ, Xiao, K	Science	2008
24302888	Activation of Smurf E3 ligase promoted by smoothened regulates hedgehog signaling through targeting patched turnover Wang, H, Liu, F, Sun, L, Chen, Z, Lv, X, Zhu, Y, Huang, S, Sun, Q, Lu, Y, Tao, Y, Zhang, C, Zhao, Y, Zhang, J, Zhang, Z, Yang, S, Zheng, X, Chen, D	PLoS Biol.	2013
10966113	Hedgehog induces opposite changes in turnover and subcellular localization of patched and smoothened Cohen, SM, Denef, N, Neubüser, D, Perez, L	Cell	2000
17641202	Patched1 regulates hedgehog signaling at the primary cilium Milenkovic, L, Rohatgi, R, Scott, MP	Science	2007